Synthesis of Cisplatin(IV) Prodrug-Tethered CuFeS₂ Nanoparticles in Tumor-Targeted Chemotherapy and Photothermal Therapy

Abstract

In this study, for the first time, CuFeS nanocrystals were successfully prepared through a facile noninjection-based synthetic strategy, by reacting Cu and Fe precursors with dodecanethiol in a 1-octadecene solvent. This one-pot noninjection strategy features easy handling, large-scale production, and high synthetic reproducibility. Following hyaluronic acid (HA) encapsulation, CuFeS nanocrystals coated with HA (CuFeS@HA) not only readily dispersed in water and showed improved biocompatibility but also possessed a tumor-specific targeting ability of cancer cells bearing the cluster determinant 44 (CD44) receptors. The encapsulated CuFeS@HA showed broad optical absorbance from the visible to the near-infrared (NIR) region and high photothermal conversion efficiencies of about 74.2%. They can, therefore, be utilized for the photothermal ablation of cancer cells with NIR light irradiation. In addition, toxicity studies in vitro (B16F1 and HeLa) and in vivo (zebrafish embryos), as well as in vitro blood compatibility studies, indicated that CuFeS@HA show low cytotoxicity at the doses required for photothermal therapy. More importantly, CuFeS@HA can be used as delivery vehicles for chemotherapy cisplatin(IV) prodrug forming CuFeS@HA-Pt(IV). Their release profile revealed pH- and glutathione-mediated drug release from CuFeS@HA-Pt(IV), which may minimize the side effects of the drug to normal tissues during therapy. Subsequent in vitro experiments confirmed that the use of CuFeS@HA-Pt(IV) provides an enhanced and synergistic therapeutic effect compared to that from the use of either chemotherapy or photothermal therapy alone.

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

“…PTT uses photon energy to heat tumors physically, but PDT utilizes photosensitizers (PSs) to generate cytotoxic reactive oxygen species (ROS) and induce cancer cell death [111]. Phototherapies exhibit several advantages over traditional radiotherapy and chemotherapy, including their noninvasive nature, high selectivity, and a low number of side effects [112,113]. However, single phototherapy cannot completely eradicate a tumor because the laser intensity inevitably decays with the depth of the biological tissue, and the uneven distribution of the heat generated in the tissue damages normal tissues [114,115].…”

“…PTT uses photon energy to heat tumors physically, but PDT utilizes photosensitizers (PSs) to generate cytotoxic reactive oxygen species (ROS) and induce cancer cell death [111]. Phototherapies exhibit several advantages over traditional radiotherapy and chemotherapy, including their noninvasive nature, high selectivity, and a low number of side effects [112,113]. However, single…”

Nanomaterial‐mediated platinum drug‐based combinatorial cancer therapy

“…CuFeS 2 ‐CS‐Pt with irradiation achieved remarkable anticancer effects in mice bearing A549 tumor, and the tumor was eliminated completely in two of four mice. Chang et al coated CuFeS 2 with HA and loaded DSCP to yield CuFeS 2 @HA‐Pt(IV) for combinatorial therapy 68 . The hybrid displayed a superior high photothermal conversion efficacy of 74.2% and significantly inhibited B16F1 cancer cell proliferation.…”

Synthesis strategies and application of ternary quantum dots — in cancer therapy

“…CIS QDs bonded with doxorubicin (DOX), an anti-cancer drug was reported to effectively deliver DOX to the targeted cancer cells [59]. In another study, Girma et al [126] described the conjugation of synthesised CuFeS 2 NPs with anti-cancer drug cisplatin (IV). The study revealed that the CuFeS 2 NPs drug conjugate reduced the side effect of the drug on normal tissues.…”